NL7906424A - TRICHLOROPHENOXYALKANCARBONIC ACIDS FREE OF CHLORORATED DIBENZO-P-DIOXYNES. - Google Patents

Description

if r PPG Industries, Inc., of Pittsburgh, Pennsylvania, USA St. America

Trichlorophenoxyalkane carboxylic acids free from chlorinated dibenzo-p-dioxins.

The invention relates to trichlorophenoxyalkane carboxylic acids which are free from chlorinated dibenzo-p-dioxins.

2.4.5- Trichlorophenoxyalkane carboxylic acids, in particular 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2- (2,4,5-trichlorophenoxy) -propionic acid (Silvex, trade name) and the salts, aliphatic esters and amides thereof are known as particularly effective herbicides.

2.4.5- Trichlorophenoxyalkanecarboxylic acid, eg 2,4,5-T, is typically prepared by condensing 2,4,5-trichlorophenol with haloalkanecarboxylic acid, eg monochloroacetic acid in aqueous alkali metal hydroxide solution, as described for example in

U.S. Patent 2,598,692. It is also known to prepare 2,4,5-trichloro-phenoxyalkanecarboxylic acid, e.g., 2,4,5-T, by chlorinating the sodium salt of 2,5-dichlorophenoxyacetic acid, such as described, for example, in U.S. Patent 2,717,907.

The use of both 2,4,5-T and Silvex has been severely limited by a recent "Environmental Protection Agency" regulation because these materials each contain trace amounts of chlorinated dibenzo-p-dioxynes, especially 2,3,7 8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), which is formed as a by-product in the preparation of 2,4,5-T and Silvex.

2,3,7,8-TCDD is particularly toxic and there is some evidence that it can be fatal for certain species of laboratory animals at levels as low as 0.6 / tm / kg body weight.

Methods have been developed to treat 2,4,5-T or Silvex to reduce their 2,3,7,8tTCDD content, and these methods are described, for example, in U.S. Patents 4,026,917 and 3,840,593. In U.S. Patent 4,026,917, the dioxide is removed from 2,4,5-T by adsorption of the dioxide with coconut charcoal. This method is said to reduce the dioxide content of 2,4,5-T to less than 1 ppm In U.S. Pat. No. 3,840,593, Silvex is subjected to fractional liquid-liquid extraction with a polar liquid solvent, which is reported to reduce the Silvex's dioxide content to typically less than 0.1 ppm. However, such treatment methods, although removing some of the dioxide from 2,4,5-T or Silvex, cause the problem of getting rid of the treatment material contaminated with the dioxide, that is, the charcoal in the case of U.S. Pat. No. 4,026,917 and the solvent in the case of U.S. Patent No. 3,840,593. In other words, such methods focus only on the symptoms rather than the cause. In addition, detectable amounts of dioxide remain in the treated 2,4,5-T and the Silvex.

Before this invention was made, trichlorophenoxyalkane carboxylic acids, for example 2,4,5-T, Silvex and hydrolyzable derivatives thereof, were free from detectable amounts of chlorinated dibenzo-p-dioxynes, especially 2,3,7,8-TCDD unknown, because previous methods have provided known product containing varying amounts, although in some cases small amounts, of chlorinated dibenzo-p-dioxins,

For example, current preparation processes are believed to provide 2,4,5-T that is only 0.01 parts by weight.

2.3.7.8- TCDD contains per million parts, 2,4,5-T, Although 10 parts. However, per 25 billion 2,3,7,8-TCDD in 2,4,5-T seem negligible for all practical purposes, due to the particularly toxic nature of 2.3.7.8-TCDD, material containing even such low levels becomes considered potentially dangerous,

The invention provides as new products 2,4,5-30 trichlorophenoxyacetic acid (2,4,5-T) and 2- (2,4,5-trichlorophenoxy) propionic acid (Silvex), including the hydrolyzable salts, aliphatic esters and amides of these acids, these products being free from chlorinated dibenzo-p-dioxynes.

In accordance with the invention, the following compounds are provided 7906424 at 3 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) including hydrolyzable salts, aliphatic esters and amides thereof, this acid as well as its hydrolyzable salts , aliphatic esters and arides, are free from chlorinated dibenzo-p-dioxins; and 5 2- (2,4,5-trichlorophenoxy) propionic acid (Silvex), including hydrolysable salts, aliphatic esters and amides thereof, the acid and its hydrolysable salts, aliphatic esters and amides being free from chlorinated dibenzo-p dioxins.

The exception of the salts, the dioxyne-free compounds of the invention can be represented by formula. 1, wherein R is hydrogen or a methyl group; and Y is a hydroxy group or a hydrolyzable substituent consisting of an aliphatic group of at most 20 carbon atoms, amide, or mono- or di-substituted amide, wherein the substituent contains at most 20 carbon atoms. If Y is an aliphatic group, it is preferably an alkoxy or alkoxy-alkoxy group having up to 8 carbon atoms, and some examples thereof are ethoxy, butoxy, butoxyethoxy, isooctoxy. When Y is a mono- or di-substituted amide, the substituent is preferably an alkyl or alkoxy group having up to 8 carbon atoms. Preferably Y is either a hydroxy-20 group or a short chain alkoxy or alkoxy-alkoxy group, i.e. the respective trichlorophenoxyalkanecarboxylic acid or an ester thereof, the latter of which can be hydrolyzed to the free acid, the free acid being readily converted in the salt form, by reaction with an organic or inorganic base.

The compounds according to the invention are free from chlorinated dibenzo-p-dioxins and in particular 2,3,7,8-tetrachloro-dibenzo-p-dioxins. By “free of chlorinated dibenzo-p-dioxyne” it is meant that these dioxins cannot be detected with the known analytical techniques. For example, in 2,4,5-T and 2,4,5-T ethyl ester according to the invention 2 , 3,7,8-TCDD cannot be detected in a content of less than 4 parts by weight, 2,3,7,8-TCDD per trillion parts by weight.

2,4,5-T or 2,4,5-T ethyl ester.

The 2,4,5-trichlorophenoxyalkane carboxylic acid esters according to the invention are prepared by liquid phase alkaline condensation of 2,5-dichlorophenol with an α-haloalkane carboxylic acid ester in a 7906424 * 4 organic solvent under mild temperature conditions, that is to say » at a temperature of no more than 60 ° C, and preferably no more than 40 ° C, to prepare 2,5-dichlorophenoxyalkanecarboxylic acid ester, which is then chlorinated in the liquid phase, where a chlorine 5 atom is the hydrogen atom on the 4 substitute for the phenoxy substituent. * The 2,4,5-trichlorophenoxyalkanecarboxylic acid ester can be hydrolyzed to the 2,4,5-trichlorophenoxyalkanecarboxylic acid, which can be optionally converted to the salt form by reaction with an organic or inorganic base.

Similarly, the 2,4,5-trichlorophenoxycarboxylic acid amides of the invention are prepared by liquid phase alkaline condensation of 2,5-dichlorophenol with a 1-haloalkane-carboxylic acid amide in an organic solvent at a temperature of not more than 60 ° C, preferably not more than 40 ° C, to prepare 2,5-dichloro-15-phenoxyalkanecarboxylic acid amide which is chlorinated in the liquid phase to 2,4,5-trichlorophenoxyalkanecarboxylic acid amide. The 2,4,5-trichlorophenoxycarboxylic acid amide can be hydrolyzed to 2,4,5-trichlorophenoxyalkanecarboxylic acid, which in turn can be converted into the salt form by reaction with an organic or inorganic base.

The reaction sequence described above can be explained as follows.

1. Preparation of 2,5-dichlorophenoxyalkane carboxylic acid ester or amide is carried out according to scheme A.

2. Preparation of 2,4,5-trichlorophenoxyalkanecarboxylic acid ester or amide is carried out according to scheme B.

3. Preparation of 2,4,5-trichlorophenoxyalkanecarboxylic acid is carried out according to scheme C.

In the formulas in Schemes Af B and C, X is halogen, for example bromine, chlorine or iodine, R 'is hydrogen or a methyl group and Z is either a hydrolysable aliphatic group with up to 20 carbon atoms, preferably an alkoxy or alkoxy- akoxy group with up to 8 carbon atoms, an amide or mono- or di-substituted amide, wherein the substituent contains up to 20 carbon atoms, and preferably is an alkyl or alkoxy group with up to 8 carbon atoms.

It is believed that too high a temperature, too strong an alkaline reaction medium, or a combination of both provides an environment that leads to the condensation of chlorinated phenols with each other to form chlorinated dibenzo-p-dioxins. Therefore, it is essential in reaction 1 that the temperature is not more than 60 ° C and preferably not more than 40 ° C. It has been observed that reaction 1 proceeds favorably at room temperature, i.e. 20-23 ° C. Although temperatures below 20 ° C can be used, i.e. around 0 ° C, too low a temperature leads to an excessively prolonged reaction time.

In reaction 1, equimolar amounts of 2,5-dichlorophenol and the α-haloalkanecarboxylic acid ester or amide and base are preferably used, although a molar excess of up to 10% of the α-halogen compound is used to ensure complete reaction of the phenol group -thing is typically used. A slight molar excess of base can be used, ie, up to 5%, with care being taken to avoid excess base of much more than 5% molar excess.

Both inorganic and organic bases can be used. Examples of suitable inorganic bases are the alkali and alkaline earth metal hydroxides, such as sodium hydroxide, potassium hydroxide and calcium hydroxide. Examples of organic bases are aliphatic amines such as methyl-20 amine, dimethylamine, trimethylamine, ethylamine, diethylamine, tetraethylamine, pyridine or Ν, Ν-dimethylaniline. The alkali metal hydroxides are preferably used.

Reaction 1 is performed in an anhydrous or aqueous organic solvent. Preferred solvents are alkyl alcohols, such as ethanol, n-propanol, isopropanol, isobutanol, n-butanol. When preparing 2,5-dichlorophenoxyalkane carboxylic acid ester, the alcohol used as solvent preferably corresponds to the desired ester. For example, when the ethyl ester of 2,5-dichlorophenoxyacetate is prepared by condensing 2,5-dichlorophenol with, for example, ethyl bromoacetate, the reaction is preferably conducted in ethanol as a medium. Examples of other solvents that can be used as medium for reaction 1 are acetone, tetrahydrofuran, dimethylformamide and dimethyl sulfoxide.

Chlorination of the 2,5-dichlorophenoxyalkane-carboxylic acid ester or the 2,5-dichlorophenoxyalkane-carboxylic acid amide (reaction 2) is typically carried out in a manner known per se in a liquid solvent, for example carbon tetrachloride, either in the absence of a catalyst or in the presence of a suitable catalyst, such as iodine, metallic iron or tin, or iron (lil) chloride.

Hydrolysis of the 2,4,5-trichlorophenoxyalkanecarboxylic acid ester or the 2,4,5-trichlorophenoxyalkanecarboxylic acid amide to the free acid can be carried out in a manner known per se, for example by treating the amide or the ester with an aqueous solution of an alkali metal hydroxide or an aqueous solution of a mineral acid. Conversion of the free acid to its corresponding metal salts or amine salts can be accomplished in a known manner by reacting the acid with an inorganic or organic base, such as the bases discussed above in the discussion. of reaction 1 have been reported.

The 2,5-dichlorophenol used as starting material in the preparation of the compounds of the invention should be as pure as possible and substantially free of 2,4-dichlorophenol and other chlorinated isomers. The 2,5-dichlorophenol should be at least 99% pure and preferably at least 99.5% pure.

The 2,5-dichlorophenol can be prepared by methods known in the art, such as, for example, alkaline hydrolysis of 1,2,4-trichlorobenzene. A particularly preferred method of preparing 2,5-dichlorophenol is to react the sulfate salt of 2,5-dichloroaniline with alkali metal nitrite, for example sodium nitrite, followed by hydrolysis of the diazonium salt.

The invention is further elucidated by means of the example below.

Example 30 1. Preparation of 2,5-dichlorophenol.

145 g (0.895 mol) of solid 2,5-dichloroaniline are added to 400 ml of concentrated sulfuric acid in a 2 l flask over a period of 5 min. During the addition period, the solution exothermically reached a temperature of 60 ° C. The sulfate salt solution of 2,5-dichloro-aniline was cooled in an ice bath to about 5 ° C and a solution 7906424 7 of 65.6 g (0.98 mol) vacuum-dried sodium nitrite in 400 ml of concentrated sulfuric acid was added at such a rate that no exotherm occurred. The mixture was stirred at 0-5 ° C for 30 min, warmed to room temperature and stirred for an additional hour. 450 ml of water were slowly added to the stirred mixture and the diluted mixture was stirred for 15 min.

subjected to steam distillation. An additional 450 ml of water was added slowly and the mixture was subjected to steam distillation for 75 min. The head temperature at the start of the distillation was 145 ° C, the head temperature at the completion of the distillation was 125 ° C, and the pot end temperature was 157 ° C. The distillate was transferred to a separatory funnel and extracted with 300 ml portions of methylene chloride, 200 ml and 100 ml. The extracts were combined and concentrated on a rotary evaporator at 55 ° C and 40 mm Hg to remove methylene chloride. 135 g corresponding to a 92% yield, slightly orange-colored 2,5-dichlorophenol were thus obtained.

2. Preparation of the ethyl ester of 2,5-dichlorophenoxyacetate.

In a 1000 ml three-necked flask equipped with a mechanical stirrer and reflux condenser, 130.4 g (0.8 mol) of 20 2,5-dichlorophenol (prepared as described in step 1) were dissolved in 300 ml of absolute, that is, anhydrous, ethanol. 32.4 g (0.81 mol) of sodium hydroxide, dissolved in 300 ml of absolute ethanol, were added to the phenol solution at room temperature. The resulting mixture was stirred for 30 min and then 133.6 g (0.8 mole) of ethyl bromoacetate 25 were added over a period of 15 min. The resulting mixture was stirred at room temperature, that is to say about 23 ° C, for 30 h. (After stirring for 1 hour, a white precipitate, believed to be sodium bromide, was observed). After stirring was completed, the mixture was filtered and the filtrate was concentrated on a rotary evaporator at 55 ° C, 140 mm Hg and suspended solids containing liquid was obtained. Both the liquid and the solids were taken up in 200 ml of carbon tetrachloride and transferred to a separatory funnel. The mixture was washed 2 times with 50 ml portions of sodium hydroxide solution and 1 time with 50 ml water. After washing, the organic phase was separated, dried over magnesium sulfate, filtered and the 7906424 8 filtrate was concentrated on a rotary evaporator at 55 ° C, 140 mm Hg to give a red-yellow liquid. The liquid was taken up in 150 ml of carbon tetrachloride. , treated with 2 g of activated charcoal, filtered and the filtrate was concentrated on a rotary evaporator at 55 ° C, 140 mm Hg. 190 g of a pale yellow liquid were obtained in this way, which corresponds to a 92% yield of ethyl ester of 2,5-dichlorophenoxyacetate.

3. Preparation of the ethyl ester of 2,4,5-trichlorophenoxyacetate.

To a 1000 ml three neck flask equipped with a reflux condenser, magnetic stir bar and a gas supply tube, 148.8 g (0.6 mol) of ethyl ester of 2,5-dichlorophenoxyacetate (prepared as described in step 2) were dissolved in 500 ml carbon tetrachloride, as well as 2.5 g anhydrous iron (XXI) chloride. The mixture was stirred vigorously and chlorine gas was introduced into the mixture at room temperature, that is to say about 23 ° C, for 7 hours. The chlorinated mixture was then degassed with nitrogen, filtered and the filtrate transferred to a separatory funnel. The filtrate was washed twice with 250 ml portions of hydrochloric acid and once with 250 ml water. The organic phase was separated, dried over magnesium sulfate and concentrated on a rotary evaporator at 55 ° C, 140 mm Hg. A yellow oil was obtained which, after cooling at room temperature, yielded 155 g (90% yield) of crude, chamois colored, crystalline ethyl ester of 2,4,5-trichlorophenoxyacetate.

About 18 g of the crude ethyl ester of 2,4,5-trichlorophenoxyacetate was swirled with 15 ml ethyl acetate and treated with 50 ml ligroine (petroleum ether). After evaporation of the solvent, 11 g of finely divided, pale yellow solid ethyl ester of 2,4,5-trichloro-phenoxyacetate were obtained.

4. Preparation of 2,4,5-trlchlorophenoxy-acetic acid

About 5.67 g (0.02 mol) of ethyl ester of 2,4,5-trichlorophenoxyacetate (prepared as described in step 3) were treated with 3.2 g (0.08 mol) of sodium hydroxide dissolved in 25 ml of water. The mixture was heated under reflux for 4 hours under constant stirring.

After refluxing, the mixture was cooled to 7906424, diluted with 15 ml of water and carefully poured into 50 ml of concentrated hydrochloric acid to form a white precipitate. The precipitate was separated by filtration and dried at 70 ° C in a vacuum oven. The dried precipitate was recrystallized from a mixture of 30 vol.% Ethyl acetate and 70 vol.% Ligroin to leave a white crystalline solid of pure 2,4,5-trichlorophenoxyacetic acid (mp 150-153 ° C) .

Neither 2,3,7,8-tetrachlorodibenzo-p-dioxin could be used in the ethyl ester of 2,4,5-trichlorophenoxyacetate prepared in step 3 and the 2,4,5-trichlorophenoxyacetic acid prepared in step 4. demonstrated at a content of less than 4 parts by weight. 2,3,7,8-TCDD per trillion parts. of either the ethyl ester of 2,4,5-trichlorophenoxyacetic acid or 2,4,5-trichlorophenoxyacetic acid itself.

15 7906424

Claims (12)

1. The trichlorophenoxyalkanecarboxylic acids: 2,4,5-trichlorophenoxyacetic acid and 2- (2,4,5-trichlorophenoxy) propionic acid, and the hydrolyzable salts, aliphatic esters and amides thereof, free of 5 chlorinated dibenzo-p-dioxins. 2. 2,4,5-Trichlorophenoxyacetic acid, including hydrolyzable salts, aliphatic esters and amides thereof, free from chlorinated dibenzo-p-dioxins. 3. 2- (2,4,5-Trichlorophenoxy) propionic acid, including hydrolyzable salts, aliphatic esters and amides thereof, free from chlorinated dibenzo-p-dioxins. 4. Process for the preparation of 2,4,5-trichloro-phenoxyalkanecarboxylic acid esters or amides thereof, which are free of chlorinated dibenzo-p-dioxins, characterized in that one is used in a. liquid organic solvent as reaction medium and in the presence of an organic or organic base at a temperature of not more than 60 ° C reacts 2,5-dichlorophenol with an α-halogen compound of formula 2, wherein X is bromine, chlorine or iodine, R 'is hydrogen or a methyl group and Z is a hydrolyzable group consisting of an aliphatic group with 20 at most 20 carbon atoms or an amide or mono- or di-substituted amide, wherein the substituent contains at most 20 carbon atoms; using at least 1 mole of this compound per mole of 2,5-dichlorophenol and at least 1 mole but not more than a 5% molar excess of base used per mole of 2,5-dichlorophenol, and the reaction product in the liquid phase chlorinated, Process according to claim 4, characterized in that an alkali metal hydroxide is used as the base. Process according to claim 4 or 5, characterized in that the reaction temperature of not more than 40 ° C is used. Process according to one or more of claims 4 to 6, characterized in that in the compound of formula 2 z is an alkoxy or alkoxy-alkoxy group with at most 8 carbon atoms. 8. Process according to any one of claims 4-6, characterized in that in the compound of formula 2 Z is a mono- or di-substituted amide in which the alkyl or alkoxy group contains at most 7906424 8 carbon atoms. 9. Process according to one or more of claims 4-8, characterized in that anhydrous or aqueous aliphatic alcohol is used as the reaction medium. 10. Process for preparing 2,4,5-trichlorophenoxyalkanecarboxylic acid, consisting of 2,4,5-trichlorophenoxyacetic acid or 2- (2,4,5-trichlorophenoxy) propionic acid, characterized in that the corresponding 2, 4,5-trichlorophenoxyalkanecarboxylic acid ester or the corresponding 2,4,5-trichlorophenoxyalkanecarboxylic acid amide, which is free from chlorinated dibenzo-p-dioxins, hydrolyses. 11. Process for preparing salts of 2,4,5-trichlorophenoxyalkanecarboxylic acid, consisting of 2,4,5-trichlorophenoxyacetic acid or 2- (2,4,5-trichlorophenoxy) propionic acid, characterized in that 2.4, 5-Trichlorophenoxyalkanecarboxylic acid reacts with an organic or inorganic base, this 2,4,5-trichlorophenoxyalkanecarboxylic acid being free from chlorinated dibenzo-p-dioxins. 12. A method of controlling plant growth, characterized in that a growth-controlling amount of a compound consisting of: (a) 2,4,5-trichlorophenoxyacetic acid or a hydrolyzable salt, aliphatic eater or amide thereof, free from chlorinated dibenzo-p-dioxynes: (b) 2- (2,4,5-trichlorophenoxy) propionic acid or a hydrolyzable salt, aliphatic ester or amide thereof, free of chlorinated dibenzo-p-dioxynes, or (c) mixtures thereof. 13. A process for the preparation of 2,4,5-trichloro-phenoxyalkanecarboxylic acids, salts, aliphatic esters and amides thereof, free from chlorinated dibenzo-p-dioxynes, as described herein. 7906424 r, · Cl Η O HO I II I II I 0— c - c - Y X — c — c — z * a'Y "1 2 Cl -A-". N H 0 Cl Cl I || · 1 OH H O / 0 c c z rV 1 'I base rY I, \\) _j_ X C C Z 0 solvent ^ Lj} R Cl ·' ··. * .- 'Vi.v · l vV · ν ·. '- "v: O ~ ° HO HO Cl V || Cl I || 1 0-C-C-Z + Clj _ X, 0— CCZ <rini · -c- Cl? in" f «i ^ .O - C — c— ZI o— CC - OH ju r1 h * °, nr i ZUUr ° ft) aSe ^ Cl cl T Cl 7906424 PPG Industries, Inc., Pittsburgh, Pennsylvania, United States of America